Randomized Sham-Controlled Trial Evaluating Efficacy and Safety of Endoscopic Gastric Plication for Primary Obesity: The ESSENTIAL Trial

• The ESSENTIAL trial tested a non-surgical weight loss procedure performed through the mouth using an endoscope, with no incisions or permanent digestive changes.
• This rigorous trial randomly assigned patients to real or sham procedures with blinding, ensuring results reflect true effect rather than placebo.
• Endoscopic weight loss procedures may suit patients with moderate obesity who haven't lost enough weight through diet and medications but aren't ready for surgery.
• Dr. de la Cruz-Muñoz served as a site principal investigator alongside leading researchers from Harvard and other top institutions.
• This is one of at least eight clinical trials for endoscopic and device-based weight loss therapies Dr. de la Cruz-Muñoz has participated in.
• This demonstrates offering the full range of treatment approaches from lifestyle counseling to endoscopic procedures to surgery.

Why This Study Was Needed

Many people with obesity in the BMI 30 to 40 range want more than diet and medication can deliver but are not ready for surgery. Endoscopic procedures, performed through the mouth with no incisions, aim to fill that gap. The primary obesity surgery endoluminal (POSE) procedure uses a flexible endoscope to place sutured folds (plications) in the upper stomach, reducing its capacity. Early single-center results were promising, but the field needed a rigorous, blinded trial to separate true effect from placebo and lifestyle coaching.

How the Study Was Done

The ESSENTIAL trial was a multicenter, randomized, sham-controlled study in which Dr. de la Cruz-Muñoz served as a site investigator. Adults with class I or II obesity were randomized 2:1 to the real POSE procedure (221 patients) or a sham endoscopy (111 patients). Neither patients nor the staff assessing them knew who had which. Everyone received the same low-intensity lifestyle program. The main outcomes were total body weight loss at 12 months, the share of patients losing at least 5%, and safety.

What the Study Found

• At one year, the active group lost 4.95% of total body weight versus 1.38% with sham (P < .0001).
• 41.6% of active patients lost at least 5% of their weight, compared with 22.1% after sham. Those responders lost an average of 11.5%.
• The lead-in patients treated before randomization lost 7.0%.
• No deaths or unexpected adverse events occurred. Procedure-related serious adverse events were 5.0% (active) versus 0.9% (sham), a difference that did not reach statistical significance.
• Although the procedure clearly beat sham, it did not reach the “super-superiority” margin the trial had set in advance.

What This Means for Patients

Endoscopic stomach-reduction procedures work, but the size of the effect is modest compared with surgery, and results vary widely between patients. This trial helped shape the next generation of procedures: endoscopic sleeve gastroplasty (ESG), which remodels the full length of the stomach, later achieved about 13.6% weight loss at one year in the MERIT randomized trial of endoscopic sleeve gastroplasty (Lancet, 2022). For patients with overweight or class I–II obesity, the realistic menu today includes a medical weight loss program, GLP-1 medications, intragastric balloons such as the Allurion balloon or Orbera balloon, ESG, and surgery. Our article on ESG vs. sleeve compares the main options.

Clinical Pearls

• Sham-controlled design makes this one of the highest-quality trials in endoscopic bariatric therapy.
• About 2 in 5 patients achieved at least 5% weight loss; responders averaged 11.5%.
• Safety was acceptable, with no deaths and no unanticipated adverse events.
• Results informed the shift toward full-stomach endoscopic sleeve gastroplasty.

Strengths and Limitations

Randomization, blinding and a sham control are rare in procedural trials and give these results unusual credibility. Follow-up was one year, so durability is unknown, and the lifestyle program was deliberately low-intensity. Results with POSE may not apply to newer endoscopic techniques.

Expert Commentary

A sham-controlled trial is the hardest kind of study to run in surgery and endoscopy, and the most honest. ESSENTIAL showed that endoscopic plication is safe and better than placebo, and it also showed its limits. That honesty pushed the field toward endoscopic sleeve gastroplasty, which performs better.

When patients ask me about “no-incision” options, I use trials like this to set realistic expectations: these procedures can help, especially combined with medication and good follow-up, but they are not equivalent to surgery.

— Dr. Nestor de la Cruz-Muñoz